Customized Implants For Bone Replacement

ABSTRACT

The present invention relates to customized implants for bone replacement that are prepared from poly(ether ketone ketone) or PEKK, and to a computer-based imaging and rapid prototyping (RP)-based manufacturing method for the design and manufacture of these customized implants. The PEKK customized implants made using rapid prototyping demonstrate biomechanical properties similar (if not identical) to that of natural bone even when prepared without the use of processing aids such as carbon black and aluminum powder.

TECHNICAL FIELD

The present invention generally relates to customized implants for bonereplacement that are prepared from poly(ether ketone ketone) or PEKK,and to a computer-based imaging and rapid prototyping (RP)-basedmanufacturing method for the design and manufacture of these customizedimplants.

BACKGROUND AND SUMMARY

Bone is composed of two kinds of tissue, exterior tissue which is densein texture (compact tissue) and interior tissue that consists of slenderfibers and lamellae that together form a lattice-type structure(cancellous tissue). Damage or loss of bone can result from trauma,congenital anomaly, pathologic conditions (e.g., rheumatoid arthritis,scleroderma, acromegaly and Gauchers disease), and surgical procedures.

In conventional treatment of bone defects, bone-derived or syntheticbiomaterials are used to restore form and function. These biomaterialsare preferably in the form of porous implant structures havinginterconnected porous spaces across the substratum of the implant. Thisallows bone growth into the porous spaces of the implant, securing itsincorporation and osteointegration with the surrounding or adjacentviable bone at the margins of the bone defect.

Porous implant structures may be fabricated by a number of manufacturingroutes. For implants made according to a standardized format (i.e., notcustomized fora particular individual) many conventional fabricationtechniques can be used, including casting (e.g., ceramic-mold casting,centrifugal casting, die casting, investment casting, lost foam casting,permanent-mold casting, plaster-mold casting, pressure casting, sandcasting, shell mold casting, slip casting, squeeze casting, slushcasting, vacuum casting), extrusion, laser cutting, machining (e.g.,electrochemical machining, water-jet machining), molding (e.g., blowmolding, compression molding, injection molding, powder injectionmolding), thermoforming, and the like.

Implants may also be custom designed using computer-based imaging,processing and modeling techniques to convert common medical images intocustomized 3D renderings or Computer-Aided Design (CAD) models, whichmay then be used to fabricate the implant using any number of computerdriven manufacturing techniques. The CAD models may be derived from anynumber of medical diagnostic imaging systems such as computed tomography(CT), magnetic resonance imaging (MRI), positron emission tomography(PET), and x-ray scans. Examples of computer driven manufacturingtechniques include fused deposition modeling (FDM selective lasersintering (SLS), and selective mask sintering (SMS).

Regardless of the manufacturing route, the resulting implant may then besubjected to one or more post-processing steps, which include modifyingthe implant to include pre-tab holes and other features that aid inrigid affixation.

Examples of synthetic biomaterials used in the fabrication of porousimplant structures include ceramics and polymers such as polyethylene,polytetrafluoroethylene (PTFE) and poly(ether ether ketone) (PEEK).

By the late 1990s, PEEK emerged as the leading biomaterial for implants,first being offered commercially as a biomaterial for implants in April1998. Bolstered by the existence of a stable supply of PEEK in themarketplace, research on PEEK biomaterials has and continues toflourish.

Customized PEEK scaffolds that are fabricated using CAD and rapidprototyping (RP) techniques are described in M. W. Naing et al.,FABRICATION OF CUSTOMISED SCAFFOLDS USING COMPUTER-AIDED DESIGN ANDRAPID PROTOTYPING TECHNIQUES, Rapid Prototyping Journal, vol, 11, pages249-259 (2005), In this publication, PEEK-hydroxyapatite (HAP)biocomposite blends are sintered in SLS, with the advantages of HAPreinforced PEEK composites being identified as their strength andstiffness, which are reportedly compatible to that of the bone. PEEK™150XF finely ground PEEK powder is used to make these layered scaffolds.

Unfortunately, PEEK processing temperatures are quite high. In addition,less than favorable compressive residual stress profiles have beenobserved in these customized PEEK scaffolds, attributed to therelatively high solidification rates demonstrated by PEEK materials.Moreover, achieving and maintaining homogeneity in PEEK-HAP powderblends is difficult, with a lack of homogeneity causing the formation ofHAP particle clusters in the powder blend. Localized heating of theseHAP particle clusters have been found to result in the partialdegradation of PEEK and/or the formation of microscale thermal stressesin the resulting scaffold.

By way of the present invention, it has been discovered that poly (etherketone ketone) or PEKK may be used to make customized implants for bonereplacement using rapid prototyping. PEKK offers the benefit of lowersolidification rates, and in some embodiments, may also offer the addedbenefit of considerably lower processing temperatures.

It has also been discovered that customized implants for bonereplacement that are prepared from PEKK using rapid prototypingdemonstrate biomechanical properties similar (if not identical) to thatof natural bone even when prepared without the use of processing aidssuch as carbon black and aluminum powder. In other words, these implantsmeet desired shape and strength requirements, which are typicallyexpressed in terms of geometric size and shape, minimum wall thicknessand minimum load bearing capacity.

The present invention specifically provides a laser-sinterable PEKKpowder product. The laser-sinterable powder is comprised of a PEKKcompound resin prepared from semi-crystalline and/or quasi-amorphousPEKK resin, and one or more fillers or additives selected from the groupof glass, carbon and mineral fillers. By a “semi-crystalline” or“substantially crystalline” is meant a resin which has at least 10%crystallinity as measured by DSC, preferably from about 15%-90%, andmost preferably from about 15-35% crystallinity. By “quasi-amorphous” ismeant a resin which has at most 2% crystallinity as measured by DSC. Thelaser-sinterable powder has an average particle size ranging from about10 to about 150 microns (preferably, from about 20 to about 100 microns,more preferably, from about 50 to about 70 microns).

The present invention also provides customized implants for bonereplacement that are prepared from PEKK using rapid prototyping. Thephrase “rapid prototyping”, as used herein, means the automaticconstruction of physical objects such as implants using sold freeformfabrication.

In a first contemplated embodiment, the customized implant is a rigidimplant having an inner core and an outer layer, the inner core having arelatively low porosity of less than about 10%, rendering the implantsuitable for replacing bone in load bearing applications such as thespine, long bone and hip. The inventive rigid implant demonstrates acompressive strength (ASTM #D695) or load bearing capability rangingfrom about 100 to greater than about 200 megapascals (MPa).

Preferably, at least 95% of the pores have a diameter in the range offrom about 1 to about 500 microns. Individual pores may or may not beconnected to each other.

The implant's outer layer and its inner core preferably match thecorresponding regions of the bone to be replaced if that bone werehealthy. In other words, the outer layer would approximate themorphologic traits of the compact tissue in the cortical layer of asimilar healthy bone, while the inner core would approximate themorphologic traits of the cancellous tissue in the trabecular core of asimilar healthy bone.

In a second contemplated embodiment, the customized implant is a lessrigid implant with a substantially uniform cross-sectional morphology,which has a higher porosity of greater than about 35%. Such implants aresuitable for replacing bone in partially load bearing applications suchas scaffolding for ongrowth/ingrowth of tissues, support for stem cellmedia and the like.

Preferably, individual pores in this less rigid implant are connected toeach other, the pores having a diameter in the range of from about 50 toabout 250 microns.

The present invention also provides a CAD-based RP process for thedesign and manufacture of these customized implants, the processcomprising:

-   -   (a) scanning a patient in an area requiring bone repair or        replacement to obtain tomographic information;    -   (b) designing a bone implant model at a CAD terminal using the        tomographic information obtained from the patient;    -   (c) optionally, modifying the bone implant model by, for        example, adding suture anchors, threaded holes, mating surfaces        and textures, open cell regions for scaffolding, surface pores        to carry antibiotics, and/or varying density or porosity levels        so as to vary stiffness or rigidity; and    -   (d) using a solid free-form fabrication method such as SLS to        form a bone implant from the bone implant model, the bone        implant comprising sequential layers of biocompatible PEKK.

In a preferred embodiment, a PEKK compound resin powder is used to formthe bone implant, the PEKK powder having a preferred average particlesize ranging from about 20 to about 100 microns (more preferably, fromabout 50 to about 70 microns).

In a more preferred embodiment, a SLS fabrication method is used to formthe bone implant, the SLS fabrication method comprising heating a partbed to a temperature ranging from about 280° C. to about 350° C. andscanning a 0.015 to 1.5 Wattsec/millmeter(mm)²laser spot at selectedlocations of a layer of PEKK powder contained in the part bed.

Other features and advantages of the invention will be apparent to oneof ordinary skill from the following detailed description. Unlessotherwise defined, all technical and scientific terms used herein havethe same meaning as commonly understood by one of ordinary skill in theart to which this invention belongs. All publications, patentapplications, patents and other references mentioned herein areincorporated by reference in their entirety. In case of conflict, thepresent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and notintended to be limiting.

DETAILED DESCRIPTION

Image based modeling involves three basic steps, namely, imageacquisition, image processing, and three dimensional reconstruction(3DR) to form voxels (basic unit of computed tomography reconstruction)that describe the 3D shape of the model for use in further and moreadvanced modeling, and subsequent manufacture.

As noted above, raw patient data in the form of noninvasive images ofthe area encompassing the diseased or damaged bone(s) may be acquiredfrom any number of medical diagnostic imaging systems such as CT, MRI,PET, and x-ray scans.

Image processing and 3DR may be achieved using any suitable medicalreconstructive and reverse engineering software such as MIMICS® softwareprograms for processing and editing images for medical and surgicalapplications, which are available from Materialise N.V. Technologielaan15, B-3001, Leuven, Belgium, and GEOMAGIC STUDIO® computer software forcreating digitized models, which is available from Geomagic U.S., 3200East Hwy 54, Cape Fear Building, Suite 300, Research Triangle Park,N.C., 27709.

Once loaded into the software, the raw patient data in the form ofnoninvasive images (which are typically in the form of slice images) areproperly registered and aligned. Next, the region of interest (i.e., thediseased or damaged bone(s)) is identified and a 3D rendering or modelis made. In a first contemplated embodiment, the 3D model, which is inthe form of segmented information, is further customized and thenexported to an RP machine using, for example, an RP Slice Module, whichinterfaces with MIMICS® software programs or GEOMAGIC STUDIO computersoftware and reportedly any kind of RP system. The RP Slice Module isavailable from Materialise N.V. In a second contemplated embodiment, thesegmentation is transferred directly to an RP machine.

The 3D rendering or model may be enhanced and further customized by, forexample, converting the 3D voxel dataset that describes the 3D shape ofthe model to point data form, cleaning the points (i.e., eliminatingnoise points), triangulating the points to form a faceted model, varyingdensity or porosity levels, adding open cell regions for scaffolding,modeling the bone surface using freeform surfaces or NURBS patches,further refining and enhancing the surface (e.g., adding surface poresto carry antibiotics, adding suture anchors and/or threaded holes,mating surfaces and textures), etc. Design software suitable forenhancing and further customizing the 3D rendering or model includessoftware available from SolidWorks Corporation, 300 Baker Avenue,Concord, Mass. 01742, under the trade designation SOLIDWORKS® computersoftware.

The thus generated CAD models are saved in an IGES or STEP/STL format,which are neutral data formats that allow for transfer of the 3Drendering or CAD model between dissimilar systems, and then exported toan RP machine.

In a preferred embodiment, the RP machine is a powder-based SLS system.The system, which typically comprises two side powder cartridges, aplatform with variable height, heaters and a laser source, produces 3Dobjects from sliced 3D CAD models using powdered materials with heatgenerated by the laser.

Although the CAD-based RP process for the design and manufacture ofthese customized implants will be described herein mainly in connectionwith SLS, the invention is not so limited. Other RP-based manufacturingmethods such as fused deposition modeling (FDM) and Selective MaskSintering (SMS) may be used to manufacture the inventive implant.

An SLS system suitable for use in the present invention comprises:

-   -   (a) a powder delivery system, for applying successive layers of        PEKK power onto a target surface on a variable height part bed        or platform;    -   (b) a laser for generating a laser beam;    -   (c) a scanning system for controllably directing the laser beam        to a target plane at an uppermost surface of the powder layer;        and    -   (d) a computer, coupled to the powder delivery system and        scanning system, and programmed to perform a plurality of        operations comprising: reading data from a CAD model, directing        the powder delivery system to lay down successive layers of PEKK        powder, and directing the scanning system to laser scan each        such successive PEKK layer.

Preferably, the laser for generating a laser beam in the SLS system is acarbon dioxide (CO₂) laser source. Such SLS systems are available fromEOS of North America Inc., 28970 Cabot Drive, Novi, Mich. 48377-2978,and from 3D Systems, 333 Three D Systems Circle, Rock Hill, S.C. 29730.

PEKK is used in either its pure form or with fillers or additivesselected from the group including, but not limited to, surface-bioactiveceramics (e.g., hydroxyapatite (HAp), BIOGLASS® biologically activeglass), resorbable bioactive ceramics (e.g., α-tricalcium phosphate(α-TCP), β-TCP), and solids that will render the implant or scaffoldradioopaque (e.g., barium sulfate (BaSO₄)). Processing aids such ascarbon black and aluminum powder are not employed in the subjectinvention.

In a first preferred embodiment, PEKK powder with an average particlesize ranging from about 10 to about 150 microns is used in its pureform. Such powders are available from Oxford Performance Materials,Inc., 120 Post Rd., Enfield, Conn. 06082 (“Oxford PerformanceMaterials”), under the product designation OXPEKK-IG PEKK powder.

In a second preferred embodiment, PEKK powder in the form of a compoundresin powder with an average particle size ranging from about 10 toabout 150 microns is used, the compound resin powder being prepared bymelt blending a mixture of PEKK resin with from about 10 to about 40% bywt. of one or more fillers or additives (e.g., HAp, BIOGLASS®biologically active glass, α-TCP, β-TCP, BaSO₄) using conventionalmelt-blending techniques and then grinding the blended product to form apowder.

In operation, the platform used in the SLS system is heated to atemperature ranging from about 280° C. to about 350° C. (preferably,from about 280° C. to about 295° C. (for quasi-amorphous PEKK) or fromabout 335° C. to about 350° C. (for semi-crystalline PEKK)), and a thinlayer of PEKK powder having an average particle size ranging from about10 to about 150 microns (preferably, from about 20 to about 100 microns)is spread evenly onto the heated platform with a roller mechanism. Then,the powder is raster-scanned with the CO₂ laser beam (power density(energy per unit area and time)) ranging from about 0.015 to about 1.5Wattsec/mm² (preferably, from about 0.1 to about 0.25 Wattsec/mm²), withonly the powder that is struck becoming fused. Successive layers of PEKKpowder are then deposited and raster-scanned one on top of another untilthe implant or scaffold is complete. Each layer is sintered deeplyenough to bond it to the underlying or preceding layer.

The customized implants of the present invention demonstratebiomechanical properties similar (if not identical) to that of naturalbone. More specifically, the inventive implants have a compressivestrength (ASTM #D695) or load bearing capability ranging from about 10to greater than about 200 megapascals (MPa). This compressive strengthprovides load-bearing capability greater than typical cancellous boneand up to that of typical cortical bone. The inventive implants alsohave a flexural modulus (ASTM #D570) ranging from about 0.5 to greaterthan about 4.5 gigapascals (GPa).

For implants used to replace bone in load bearing applications such asthe spine, long bone and hip, low porosity (i.e., less than about 10%)implants would be formed. These implants demonstrate compressivestrength (ASTM #D695) or load bearing capability ranging from about 100to greater than about 200 MPa and flexural modulus (ASTM #D570) rangingfrom about 3.5 to greater than about 4.5 GPa.

In one contemplated embodiment, the surface topography of the lowporosity implant is altered and/or one or more through openings areadded to encourage bone, vascular and nerve in-growth. As will bereadily appreciated by one skilled in the art, such alterations oradditions may be designed into the CAD model, or formed post-manufactureby drilling, cutting, punching, or other suitable means.

For implants used to replace bone in partially load bearing applicationssuch as scaffolding for ongrowth/ingrowth of tissues, support for stemcell media and the like, a higher porosity implant (i.e., open cell—3Dinterconnected pores) would be formed. These implants demonstratecompressive strength (ASTM #D695) or load bearing capability rangingfrom about 10 to about 200 MPa and a flexural modulus (ASTM #D570)ranging from about 0.5 to about 4.5 GPa.

In one contemplated embodiment, the higher porosity implant is in theform of a three-dimensional lattice structure. The lattice structure,which is optimized for bone, vascular and nerve in-growth, has aplurality of bars crossing each other in a plurality of zones, the barsbeing fused in each of these zones. Interstitial spaces provided betweenadjacent bars define a plurality of interconnected pores or channels inthe lattice structure.

The implant of the present invention may contain one or more porousreservoirs, which hold one or more therapeutic agents including, but notlimited to, antibiotics, anti-coagulants, anti-inflammatory,anti-metabolites, antivirals, bone morphogenic proteins, cell adhesionmolecules, growth factors, healing promotors, immunosuppressants,vascularizing agents, topical anesthetics/analgesics, and the like.These therapeutic agents may be prepared with carriers that will protectagainst rapid release (e.g., a controlled release vehicle such as apolymer, microencapsulated delivery system or bioadhesive gel). In onecontemplated embodiment, the therapeutic agent is encapsulated bybiocompatible, degradable polymers including, but not limited to,polyhydroxy acids such as polylactic acid (PLA), polyglycolic acid(PGA), and their copolymers (ALGA). These polymers are degraded byhydrolysis to products that can be metabolized and excreted.

The inventive implant may also be modified to include means for securingthe implant to adjacent bony structures. For example, interfacialfastening mechanisms such as custom mating screws and fasteners may bedesigned into the CAD model, or formed/affixed post-manufacture.

While various embodiments of the present invention have been describedabove, it should be understood that they have been presented by way ofexample only, and not limitation. Thus, the breadth and scope of thepresent invention should not be limited by any of the exemplaryembodiments.

What is claimed is:
 1. A method of forming an implant for use in amammal, the method comprising the steps of: providing a model of animplant; providing a powder comprising polyetherketoneketone (PEKK) andexcluding calcium phosphate; forming the implant by selective lasersintering the powder in accordance with the model of the implant.
 2. Themethod of claim 1, wherein the step of forming the implant by selectivelaser sintering comprises the steps of: applying a layer of the powderon a bed of a laser sintering machine; solidifying selected points ofthe applied layer of powder by irradiation in accordance with acorresponding layer of the model; successively repeating the step ofapplying the powder and the step of solidifying the applied layer ofpowder until a plurality of cross sections of the implant aresolidified.
 3. The method of claim 2, wherein the selective lasersintering further comprises the step of: maintaining a bed temperaturebetween 280 degrees Celsius and 350 degrees Celsius during thesuccessive steps of powder application and solidification.
 4. The methodof claim 2, wherein the powder comprises a semi-crystalline PEKK powderhaving a crystallinity between 15% and 90% as determined by DSC and anaverage particle size between 10 to 150 microns.
 5. The method of claim4, wherein the powder has a crystallinity between 15% and 35% asdetermined by DSC and an average particle size between 50 to 70 microns.6. The method of claim of claim 2, wherein the powder comprises aquasi-amorphous PEKK powder having a crystallinity of 2% or less asdetermined by DSC, and wherein the powder has an average particle sizebetween 50 to 70 microns.
 7. The method of claim 6, wherein theselective laser sintering further comprises the step of maintaining abed temperature between 280 degrees Celsius and 350 degrees Celsiusduring the successive steps of powder application and solidification. 8.The method of claim 2 wherein the step of selectively laser sinteringforms a mechanical fastener interface in a surface of the implant. 9.The method of claim 2 wherein the powder consists essentially of PEKK.10. The implant of claim 2, wherein the implant replaces a load-bearingbone.
 11. The implant 2, wherein the implant replaces a portion of aspine, a long bone of an arm or a leg, a hip bone, or a cranial bone.12. The method of claim 2, wherein the step of providing the modelcomprises the steps of: (a) scanning a patient to obtain tomographicinformation; (b) designing a bone implant model using from thetomographic information obtained from the patient.
 13. A method offorming an implant for use in a mammal, the method comprising the stepsof: providing a model of an implant; providing a powder formanufacturing the implant, the powder comprising a a semi-crystallinepolyetherketoneketone PEKK powder having a crystallinity between 15% and90% and excluding calcium phosphate, the powder having an averageparticle size of between 50 to 70 microns; forming the implant byselective laser sintering the powder in accordance with the implantmodel, the step of forming the implant by selective laser sinteringcomprises the following steps: applying a layer of the powder on a bedof a laser sintering machine; solidifying selected points of the appliedlayer of powder by irradiation in accordance with a corresponding layerof the model; successively repeating the step of applying the powder andthe step of solidifying the applied layer of powder until a plurality ofcross sections of the implant are solidified; maintaining a bedtemperature between 280 degrees Celsius and 295 degrees Celsius duringthe successive steps of powder application and solidification.
 14. Themethod of claim 13 wherein the step of selectively laser sintering formsa mechanical fastener interface in a surface of the implant.
 15. Themethod of claim 13 wherein the powder consists essentially of PEKK. 16.The method of claim 13, wherein the implant replaces a spine bone or acranial bone.
 17. An implant for use in a mammal, the implant comprisinglaser sintered polyetherketoneketone (PEKK) and excluding calciumphosphate.
 18. The implant of claim 17, wherein the laser sintered PEKKis prepared by applying a layer of the powder on a bed of a lasersintering machine, solidifying selected points of the applied layer ofpowder by irradiation in accordance with a corresponding layer of amodel, successively repeating the step of applying the powder and thestep of solidifying the applied layer of powder until a plurality ofcross sections of the implant are solidified.
 19. The implant of claim18, wherein a bed temperature between 280 degrees Celsius and 295degrees Celsius is maintained during the successive steps of powderapplication and solidification.
 20. The implant of claim 19 wherein theimplant comprises a mechanical fastener interface in a surface of theimplant.